BRD4 p.Pro46=
c.138G>A · VCV3710540
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0251%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -7.4 | GERP -5.2 |
| Overall | ||
| CADD | 0.998 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0251%
European (non-Finnish) · 296/1,180,000 alleles
Filtering AF
0.0227%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0217%
Overall
0.0197%
318/1,613,836 alleles · ultra-rare
exomes 311/1,461,882 · genomes 7/151,954 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0251% | 3,986 |
| East Asian | 0.0223% | 4,489 |
| Remaining individualsnot grpmax-eligible | 0.0144% | 6,943 |
| Finnishnot grpmax-eligible | 0.00156% | 63,998 |
| African / African-American | 0.00134% | 74,832 |
| South Asian | 0.0011% | 91,072 |
Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.
Variant & gene context
- Gene
- BRD4
- Protein
- p.Pro46=
- Coding
- c.138G>A
- MANE Select
- NM_001379291
- Type
- single nucleotide variant
- Location
- chr19:15272962 (GRCh38)
- Gene constraint
- LOEUF 0.191 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 56.20 · 613 PDB
- Residue 46
- the 'disordered' region; an α-helix
Similar variants
- BRD4 p.Pro46Arg Uncertain significance ★ ⚠ same residue
- BRD4 p.Pro46Ser Uncertain significance ★ ⚠ same residue
- BRD4 p.Tyr430Cys Likely pathogenic ★★ same type
- BRD4 p.Ala220Thr Uncertain significance ★★ ⚠ same type
- BRD4 p.Ala409Thr Uncertain significance ★★ ⚠ same type
- BRD4 p.Ala565Val Uncertain significance ★★ ⚠ same type
- BRD4 p.Asp337Asn Uncertain significance ★★ ⚠ same type
- BRD4 p.Asp497Gly Uncertain significance ★★ ⚠ same type
Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →
Cite Sugi Variant
Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/brd4-p-pro46 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown